Details of the Drug

General Information of Drug (ID: DMVZQ2M)

• Drug Name: Probucol
• Synonyms: Biphenabid; Bisbid; Bisphenabid; Lesterol; Lorelco; Lursell; Lurselle; Panavir; Probucolum; Sinlestal; Superlipid; Almirall Brand of Probucol; Aventis Brand of Probucol; Hoechst Brand of Probucol; DH 581; DH581; DE-3872; DH-581; LORELCO (TN); Probucolum [INN-Latin]; ZERO/001429; Probucol (JAN/USP/INN); Probucol [USAN:BAN:INN:JAN]; Acetone bis(3,5-di-tert-butyl-4-hydroxyphenyl) mercaptole; Acetone, bis (3,5-di-tert-butyl-4-hydroxyphenyl) mercaptole; Acetone, bis(3,5-di-tert-butyl-4-hydroxyphenyl) mercaptole; 2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol; 4,4'-(Isopropylidenedithio)bis(2, 6-di-tert-butylphenol); 4,4'-(Isopropylidenedithio)bis(2,6-di-tert-butylphenol); 4,4'-(Isopropylidenedithio)bis[2, 6-di-tert-butylphenol]; 4,4'-(Isopropylidenedithio)bis[2,6-di-tert-butylphenol]; 4,4'-(propane-2,2-diyldisulfanediyl)bis(2,6-di-tert-butylphenol); 4,4'-[(1-Methylethylidene)bis(thio)]bis-[2,6-bis(1,1-dimethylethyl)phenol]

Indication

Disease Entry	ICD 11	Status	REF
Coronary artery disease	BA80	Approved	[1]
Coronary heart disease	BA80.Z	Approved	[2]
Hypercholesterolaemia	5C80.0	Approved	[2]
Hyperlipidemia	5C80.Z	Approved	[2]

• Therapeutic Class: Anticholesteremic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 516.799
  Logarithm of the Partition Coefficient (xlogp); 11.3
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 12 - 500 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 27.6394 micromolar/kg/day [5]
• Chemical Identifiers:
  Formula: C31H48O2S2
  IUPAC Name: 2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol
  Canonical SMILES: CC(C)(C)C1=CC(=CC(=C1O)C(C)(C)C)SC(C)(C)SC2=CC(=C(C(=C2)C(C)(C)C)O)C(C)(C)C
  InChI: InChI=1S/C31H48O2S2/c1-27(2,3)21-15-19(16-22(25(21)32)28(4,5)6)34-31(13,14)35-20-17-23(29(7,8)9)26(33)24(18-20)30(10,11)12/h15-18,32-33H,1-14H3
  InChIKey: FYPMFJGVHOHGLL-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 4912
  ChEBI ID: CHEBI:8427
  CAS Number: 23288-49-5
  DrugBank ID: DB01599
  TTD ID: D0H2DQ
  VARIDT ID: DR01110
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ATP-binding cassette transporter A1 (ABCA1)	TTJW1GN	ABCA1_HUMAN	Modulator	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Gene/Protein Processing	[7]

Molecular Expression Atlas of This Drug

• ICD Disease Classification: 11 Disease of the circulatory system
• Disease Class: ICD-11: BA80 Coronary artery disease
• The Studied Tissue: Peripheral blood
• The Studied Disease: Coronary artery disease [ICD-11:BA80-BA8Z]

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
ATP-binding cassette transporter A1 (ABCA1)	DTT	ABCA1	4.88E-01	-0.1	-0.33

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Probucol (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Probucol and Ivosidenib.	Acute myeloid leukaemia [2A60]	[8]
Arn-509	DMT81LZ	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Arn-509.	Acute myeloid leukaemia [2A60]	[9]
Gilteritinib	DMTI0ZO	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Gilteritinib.	Acute myeloid leukaemia [2A60]	[10]
Oliceridine	DM6MDCF	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Oliceridine.	Acute pain [MG31]	[11]
Ivabradine	DM0L594	Major	Increased risk of ventricular arrhythmias by the combination of Probucol and Ivabradine.	Angina pectoris [BA40]	[9]
Dronedarone	DMA8FS5	Major	Increased risk of prolong QT interval by the combination of Probucol and Dronedarone.	Angina pectoris [BA40]	[12]
Bedaquiline	DM3906J	Major	Increased risk of prolong QT interval by the combination of Probucol and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[13]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Probucol and Levalbuterol.	Asthma [CA23]	[14]
Retigabine	DMGNYIH	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Retigabine.	Behcet disease [4A62]	[11]
Eribulin	DM1DX4Q	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Eribulin.	Breast cancer [2C60-2C6Y]	[12]
Bosutinib	DMTI8YE	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Bosutinib.	Breast cancer [2C60-2C6Y]	[9]
PF-04449913	DMSB068	Moderate	Increased risk of prolong QT interval by the combination of Probucol and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[15]
Olodaterol	DM62B78	Moderate	Increased risk of ventricular arrhythmias by the combination of Probucol and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[16]
Vilanterol	DMF5EK1	Moderate	Increased risk of ventricular arrhythmias by the combination of Probucol and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[14]
Indacaterol	DMQJHR7	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Indacaterol.	Chronic obstructive pulmonary disease [CA22]	[16]
Osilodrostat	DMIJC9X	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Osilodrostat.	Cushing syndrome [5A70]	[8]
Tetrabenazine	DMYWQ0O	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Tetrabenazine.	Dissociative neurological symptom disorder [6B60]	[12]
Deutetrabenazine	DMUPFLI	Moderate	Additive CNS depression effects by the combination of Probucol and Deutetrabenazine.	Dystonic disorder [8A02]	[17]
Ingrezza	DMVPLNC	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Ingrezza.	Dystonic disorder [8A02]	[18]
Fostemsavir	DM50ILT	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[19]
Lopinavir	DMITQS0	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Lopinavir.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Rilpivirine	DMJ0QOW	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Rilpivirine.	Human immunodeficiency virus disease [1C60-1C62]	[12]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Probucol and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[9]
Crizotinib	DM4F29C	Major	Increased risk of prolong QT interval by the combination of Probucol and Crizotinib.	Lung cancer [2C25]	[20]
Ceritinib	DMB920Z	Major	Increased risk of prolong QT interval by the combination of Probucol and Ceritinib.	Lung cancer [2C25]	[12]
Osimertinib	DMRJLAT	Major	Increased risk of prolong QT interval by the combination of Probucol and Osimertinib.	Lung cancer [2C25]	[21]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Probucol and Selpercatinib.	Lung cancer [2C25]	[22]
Lumefantrine	DM29GAD	Major	Increased risk of prolong QT interval by the combination of Probucol and Lumefantrine.	Malaria [1F40-1F45]	[23]
Hydroxychloroquine	DMSIVND	Major	Increased risk of prolong QT interval by the combination of Probucol and Hydroxychloroquine.	Malaria [1F40-1F45]	[24]
Inotuzumab ozogamicin	DMAC130	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Inotuzumab ozogamicin.	Malignant haematopoietic neoplasm [2B33]	[9]
Vemurafenib	DM62UG5	Major	Increased risk of prolong QT interval by the combination of Probucol and Vemurafenib.	Melanoma [2C30]	[12]
LGX818	DMNQXV8	Moderate	Increased risk of prolong QT interval by the combination of Probucol and LGX818.	Melanoma [2C30]	[25]
Panobinostat	DM58WKG	Major	Increased risk of prolong QT interval by the combination of Probucol and Panobinostat.	Multiple myeloma [2A83]	[26]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Probucol and Siponimod.	Multiple sclerosis [8A40]	[23]
Fingolimod	DM5JVAN	Major	Increased risk of ventricular arrhythmias by the combination of Probucol and Fingolimod.	Multiple sclerosis [8A40]	[12]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Probucol and Ozanimod.	Multiple sclerosis [8A40]	[27]
Romidepsin	DMT5GNL	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Romidepsin.	Mycosis fungoides [2B01]	[11]
Nilotinib	DM7HXWT	Major	Increased risk of prolong QT interval by the combination of Probucol and Nilotinib.	Myeloproliferative neoplasm [2A20]	[12]
Lofexidine	DM1WXA6	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Lofexidine.	Opioid use disorder [6C43]	[12]
Rucaparib	DM9PVX8	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Rucaparib.	Ovarian cancer [2C73]	[12]
Triclabendazole	DMPWGBR	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Triclabendazole.	Parasitic worm infestation [1F90]	[11]
Pimavanserin	DMR7IVC	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Pimavanserin.	Parkinsonism [8A00]	[28]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Probucol and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[29]
Degarelix	DM3O8QY	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Degarelix.	Prostate cancer [2C82]	[9]
ABIRATERONE	DM8V75C	Moderate	Increased risk of prolong QT interval by the combination of Probucol and ABIRATERONE.	Prostate cancer [2C82]	[9]
Enzalutamide	DMGL19D	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Enzalutamide.	Prostate cancer [2C82]	[9]
Iloperidone	DM6AUFY	Major	Increased risk of prolong QT interval by the combination of Probucol and Iloperidone.	Schizophrenia [6A20]	[12]
Amisulpride	DMSJVAM	Major	Increased risk of prolong QT interval by the combination of Probucol and Amisulpride.	Schizophrenia [6A20]	[30]
Asenapine	DMSQZE2	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Asenapine.	Schizophrenia [6A20]	[12]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Probucol and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[12]
Vandetanib	DMRICNP	Major	Increased risk of prolong QT interval by the combination of Probucol and Vandetanib.	Solid tumour/cancer [2A00-2F9Z]	[12]
Triptorelin	DMTK4LS	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Triptorelin.	Solid tumour/cancer [2A00-2F9Z]	[9]
Pitolisant	DM8RFNJ	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Pitolisant.	Somnolence [MG42]	[12]
Telavancin	DM58VQX	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Telavancin.	Staphylococcal/streptococcal disease [1B5Y]	[12]
Lenvatinib	DMB1IU4	Moderate	Increased risk of prolong QT interval by the combination of Probucol and Lenvatinib.	Thyroid cancer [2D10]	[12]
Cabozantinib	DMIYDT4	Major	Increased risk of prolong QT interval by the combination of Probucol and Cabozantinib.	Thyroid cancer [2D10]	[9]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7277).
• [2] Probucol FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG. Clin Sci (Lond). 2004 Aug;107(2):175-82. doi: 10.1042/CS20030351.
• [8] Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.
• [9] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [10] Product Information. Xospata (gilteritinib). Astellas Pharma US, Inc, Deerfield, IL.
• [11] Iannini PB "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf 1 (2002): 121-8. [PMID: 12904146]
• [12] Canadian Pharmacists Association.
• [13] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [14] Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
• [15] Product Information. Daurismo (glasdegib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [16] Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
• [17] Product Information. Austedo (deutetrabenazine). Teva Pharmaceuticals USA, North Wales, PA.
• [18] Product Information. Ingrezza (valbenazine). Neurocrine Biosciences, Inc., San Diego, CA.
• [19] Product Information. Rukobia (fostemsavir). ViiV Healthcare, Research Triangle Park, NC.
• [20] Product Information. Xalkori (crizotinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [21] Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
• [22] Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
• [23] Cerner Multum, Inc. "Australian Product Information.".
• [24] Harper KM, Knapp DJ, Criswell HE, Breese GR "Vasopressin and alcohol: A multifaceted relationship." Psychopharmacology (Berl) 235 (2018): 3363-79. [PMID: 32936259]
• [25] Product Information. Braftovi (encorafenib). Array BioPharma Inc., Boulder, CO.
• [26] Product Information. Farydak (panobinostat). Novartis Pharmaceuticals, East Hanover, NJ.
• [27] Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
• [28] Product Information. Nuplazid (pimavanserin). Accelis Pharma, East Windsor, NJ.
• [29] Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
• [30] Product Information. Barhemsys (amisulpride). Acacia Pharma, Inc, Indianapolis, IN.